Project Summary We are developing an improved clinical method to treat patients with malignant pleural effusions. A pleural effusion is an abnormal build-up of fluid in the pleural cavity, the fluid space that surrounds the lungs. These malignant pleural effusions (MPE) occur in 150,00-175,000 patients in the US each year, affecting between 7 to 15% of all cancer patients. Management of a MPE is palliative and typically involves drainage of the accumulated fluid followed by either placement of a long term drainage catheter or a procedure to induce obliteration of the potential pleural space through inflammation and adhesion formation termed pleurodesis. The simplest and least invasive procedure is tube thoracostomy with chemical pleurodesis. The main problem with the current techniques is its frequent clinical secondary failure rate due to the inefficient and non-uniform distribution of the sclerosing agent. Our overarching Phase I Specific Aims are focused on the development of an improved clinical approach to administering the sclerosing agent to overcome the problems with the current clinically practiced methods. Specific aims of this proposal are: Specific Aim 1: Develop three optimized talc formulations with the newly-developed biocompatible hydrogel, TRI-726 and demonstrate a uniform dispensing distribution of the resulting foaming Hydrogel + talc formulation in combination with and without a propellant. Specific Aim 2: Demonstrate feasibility of the approach in an animal model of pleurodesis. Impact and Future Studies: By providing a novel improved procedure to administer a sclerosing agent we expect to provide a more uniform dispersion of the agent with prolonged contact time that avoids reagent pooling that results in poor efficacy. This approach is expected to significantly impact the current clinical standard of care and result in markedly improved clinical outcomes with a simple, minimally invasive procedure.